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<p>Functionalized γ-lactones and cyclopropanes, especially those bearing amide substituents, play important roles in diverse chemical and pharmacological processes, but their synthesis remains challenging. Here, we report a high-throughput protocol that employs amide-sulfoxonium ylides as versatile C1 synthons in efficient [1 + 4] and [1 + 2] annulation reactions with readily available alkene derivatives, delivering a variety of (hetero)amide-substituted γ-lactones and cyclopropanes in good yields. This simple approach demonstrates a broad substrate scope, high functional group compatibility, and excellent chemo- and diastereoselectivity, and can even be utilized for the late-stage diversification of complex bioactive molecules. Combined with machine learning, a yield predictive model for cyclopropane formation is established. Mechanistically, both [1 + 4] and [1 + 2] annulations are initiated by intermolecular Michael addition, diverging into selective 5-<i>exo-trig</i> and 3-<i>exo-trig</i> cyclization, respectively. Moreover, these synthetic transformations provide a reliable and efficient route to complex γ-lactones and cyclopropanes that are otherwise difficult to access.</p>

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Divergent synthesis of γ-lactones and cyclopropanes via efficient [1 + 4] and [1 + 2] annulations of amide-sulfoxonium ylides

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月16日

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  • Yougen Xu,
  • Haiting Wu,
  • An Lin,
  • Shuang Luo,
  • Lebin Su

摘要

Functionalized γ-lactones and cyclopropanes, especially those bearing amide substituents, play important roles in diverse chemical and pharmacological processes, but their synthesis remains challenging. Here, we report a high-throughput protocol that employs amide-sulfoxonium ylides as versatile C1 synthons in efficient [1 + 4] and [1 + 2] annulation reactions with readily available alkene derivatives, delivering a variety of (hetero)amide-substituted γ-lactones and cyclopropanes in good yields. This simple approach demonstrates a broad substrate scope, high functional group compatibility, and excellent chemo- and diastereoselectivity, and can even be utilized for the late-stage diversification of complex bioactive molecules. Combined with machine learning, a yield predictive model for cyclopropane formation is established. Mechanistically, both [1 + 4] and [1 + 2] annulations are initiated by intermolecular Michael addition, diverging into selective 5-exo-trig and 3-exo-trig cyclization, respectively. Moreover, these synthetic transformations provide a reliable and efficient route to complex γ-lactones and cyclopropanes that are otherwise difficult to access.